The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus
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Burlock, Brianna; Richardson, Gabrielle; García Rodríguez, Sonia; Olivares Guerrero, Salvador; Zubiaur, Mercedes; Sancho, JaimeEditorial
MDPI
Materia
Bregs CD38 CD1dhi lupus IL-10 Autoimmunity Inflammation
Date
2018-09-25Referencia bibliográfica
Burlock, B. [et al.]. The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus. Int. J. Mol. Sci. 2018, 19, 2906; doi:10.3390/ijms19102906.
Sponsorship
Work performed in the Sancho and Zubiaur labs was supported in part by the European Commission in collaboration with the following Funding Agencies: (i) Junta de Andalucía, Consejería Innovación Ciencia y Empresa y Consejería Educación y Ciencia, Project: PC08-CTS-04046 to Jaime Sancho and Mercedes Zubiaur, and (ii) Ministerio de Economía y Competitividad (MINECO), Projects: SAF-2011-27261 and SAF-2017-89801-R to Jaime Sancho and Mercedes Zubiaur. The stay of B.B. and G.R. in Sancho’s lab was supported by National Science Foundation: Grant #HRD-0963629 (G-STEM). USA.; and U.S. Department of Education; Student Aid and Fiscal Responsibility Act; Title III Grant (SAFRA, Part F). Grant SAF-2017-89801-R covers in part the costs to publish in open access.Abstract
Previous work from our group has shown that Cd38-/- mice develop a milder
pristane-induced lupus disease than WT or Art2-/- counterparts, demonstrating a new role for
CD38 in promoting aberrant inflammation and lupus-like autoimmunity via a Transient Receptor
Potential Melastatin 2 (TRPM2)-dependent apoptosis-driven mechanism. In this study we asked
whether CD38 may play a role in the expression and function of regulatory B cells (IL-10-producing
B cells or B10 cells). In pristane-treated mice the frequency of spleen CD19+CD1dhiCD5+ B cells,
which are highly enriched in B10 cells, was significantly increased in Cd38-/- splenocytes compared
to WT, while the frequency of peritoneal plasmacytoid dendritic cells (pDCs), which are major type I
Interferon (IFN) producers, was greatly diminished. The low proportion of pDCs correlated with
lower amounts of IFN-α in the peritoneal lavage fluids of the Cd38-/- mice than of WT and Art2-/-
mice. Functional ex vivo assays showed increased frequencies of IL-10-producing B cells in Cd38-/-
splenocytes than in WT upon stimulation with an agonist anti-CD40 mAb. Overall these results
strongly suggest that Cd38-/- mice are better suited than WT mice to generate and expand regulatory
B10 cells following the appropriate stimulation.